NOTE pubs.acs.org/joc
Synthesis of Unsymmetrical Sulfides Using Ethyl Potassium Xanthogenate and Recyclable Copper Catalyst under Ligand-Free Conditions Vijay Kumar Akkilagunta and Rama Rao Kakulapati* Organic Chemistry Division-I, Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad 500607, India
bS Supporting Information ABSTRACT: The synthesis of unsymmetrical sulfides has been achieved in good to excellent yields with inexpensive ethyl potassium xanthogenate via cross-coupling reaction using recyclable CuO nanoparticles under ligandfree conditions.The copper oxide nanoparticles can be recovered and reused up to five cycles without loss of activity.
T
he construction of biological and synthetically important CS bond through cross-coupling reactions using various transition metals such as Pd,1 Cu,2 Fe,3 Co,4 In,5 Ni,6 etc. has been well explored over the years owing to various developments in the area of cross-coupling reactions. Most of these methods require metal reagents in combination with different ligands for achieving smooth conversions. The disadvantages, like metal accumulations and organic waste generation associated with these methods, make them less adoptable for the sustainable synthesis of various sulfide molecules. In view of these drawbacks, the development of efficient protocols using recyclable catalysts devoid of ligands would address the problems associated with the metal accumulation and toxic waste generation in the environment. This is the main focus in the current organic research due to the growing concern for sustainable chemistry. Cross-coupling reactions using copper oxide nanoparticles (CuO nps) have the advantages of recyclability and absence of external ligands that minimize the organic waste generation as compared with the conventional catalytic systems. So in continuation of our sustainable approach using CuO nps for cross-coupling reactions,7 we report herein the synthesis of unsymmetrical sulfides utilizing ethyl potassium xanthogenate,8 CuO nps, and aryl halides under ligand-free conditions. Initially, we studied the reaction of phenyl iodide with potassium ethyl xanthogenate for the formation of diaryl sulfide in DMSO at 85 °C. Phenyl iodide reacted completely within 15 h as monitored by GC to form phenylxanthogenate ester in situ, which, upon addition of KOH and 4-methyliodobenzene, afforded the CS cross-coupled product (summarized in Table1). The solvents like 1,4-dioxane, toluene, NMP, DMF, and acetonitrile, in combination with the bases such as Cs2CO3, Li2CO3, K2CO3, Na2CO3, t-BuOK, and t-BuOLi, were found to be inefficient in achieving a good conversion of the coupled product. We observed 97% yield of the aryl sulfide formation with DMSO and KOH as the solvent and base, respectively. The optimum amount of CuO required was found to be 7 mol % to obtain the maximum yield of the coupled product, whereas nearly the same yield was obtained when 10 and 7 mol % of CuO was used. r 2011 American Chemical Society
However, 5 mol % resulted in a slight decrease in the yield, and hence, 7 mol % of the catalyst was used for further reactions. The catalytic activity of bulk CuO as catalyst was significantly low as compared to the CuO nps (19, Table 1). From this we infer that the reaction might be taking place over the surface of the nanoparticles, whereas the reaction did not take place in the absence of the copper catalyst (18, Table 1). This has clearly proved that the presence of a copper catalyst was crucial for the reaction.9 We further tested various aryl halides viz. bromo- and iodobenzenes with the optimized conditions. The yields of aryl sulfides after two iterations were remarkably high with aryl iodides when compared to aryl bromides (Table 2, entries 1, 2). Unfortunately, the yields of the coupling between Ar-Br and Ar0 -Br are discouraging (Table 2, entry 3). Aryl iodides with different substituents like nitro, methoxy, isopropyl, tert-butyl, chloro, and fluoro were tested for their reactivities. The reaction of 4-nitroiodobenzene was faster as expected followed by chloro, fluoro, alkyl, and methoxy substituents, which after the second iteration with the respective aryl halides, gave good to excellent yields of the coupled products (Table 2). Moreover, the double thiolation of p-diiodobenzene required 2 equiv each of xanthogenate, KOH, and iodobenzene to form the desired cross-coupled product in 78% yield (entry 6, Table 2). We also succeeded in obtaining the heterothioethers in moderate yields with 2-bromothiophene and 2-bromopyridine in 73% and 66% yields, respectively (entries 14 and 15, Table 2). To broaden the substrate scope, we investigated the synthesis of various thioethers using alkyl halides in the second iteration. Interestingly, alkyl halides such as cyclohexyl-, n-hexyl-, n-pentyl-, n-decyl-, and 2-bromoethanol gave the desired products in moderate to excellent yields. Nevertheless, the yields of the products were moderate in the case of 2-bromonaphthalene with both aryl and alkyl halides (Tables 2 and 3). To expand the utility of this methodology, a reaction on a higher scale was performed Received: April 21, 2011 Published: July 06, 2011 6819
dx.doi.org/10.1021/jo200793k | J. Org. Chem. 2011, 76, 6819–6824
The Journal of Organic Chemistry
NOTE
Table 1. Optimization of Solvents and Bases for CuO Nano Catalyzed Synthesis of Thioethersa
entry
copper
solvent
base
yield (%)
1
CuO nano
DMF
KOH
2
CuO nano
dioxane
KOH
75
3
CuO nano
DMSO
K2CO3
43
4 5
CuO nano CuO nano
DMSO DMSO
Li2CO3 t-BuOK
38 58
6
CuO nano
DMSO
t-BuOLi
55
7
CuO nano
DMSO
K3PO4
46
8
CuO nano
DMSO
KOH
95b
9
CuO nano
DMSO
KOH
97c
10
CuO nano
DMSO
KOH
89d
88
11
CuO nano
DMSO
Cs2CO3
32
12 13
CuO nano CuO nano
DMF THF
Cs2CO3 KOH
24 29
14
CuO nano
CH3CN
KOH
25
15
CuO nano
Toluene
KOH
14
16
CuO nano
NMP
KOH
67
17
CuO nano
18 19
CuO
H2 O
KOH
DMSO
KOH
